Downregulated brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 inhibits osteogenesis of BMSCs through p53 in type 2 diabetes mellitus.

ABSTRACT: The bone marrow mesenchymal stem cells (BMSCs)-mediated abnormal bone metabolism can delay and impair the bone remodeling process in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that the downregulation of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), a circadian clock protein, inhibited the Wnt/β-catenin pathway via enhanced GSK-3β in diabetic BMSCs. In this article, we confirmed that the downregulated BMAL1 in T2DM played an inhibitory role in osteogenic differentiation of BMSCs. Upregulation of BMAL1 in the diabetic BMSCs significantly recovered the expression pattern of osteogenic marker genes and alkaline phosphatase (Alp) activity. We also observed an activation of the p53 signaling pathways, exhibited by increased p53 and

SUBMITTER: Mao X 

PROVIDER: S-EPMC7358138 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature